Skip to main content

Surrogate outcomes in health technology assessment: An international comparison

  • Marcial Velasco Garrido (a1) and Sandra Mangiapane (a2)

Objectives: Our aim was to review the recommendations given by health technology assessment (HTA) institutions in their methodological guidelines concerning the use of surrogate outcomes in their assessments. In a second step, we aimed at quantifying the role surrogate parameters take in assessment reports.

Methods: We analyzed methodological papers and guidelines from HTA agencies with International Network of Agencies for Health Technology Assessment membership as well as from institutions related to pharmaceutical regulation (i.e., reimbursement, pricing). We analyzed the use of surrogate outcomes in a sample of HTA reports randomly drawn from the HTA database. We checked methods, results (including evidence tables), and conclusions sections and extracted the outcomes reported. We report descriptive statistics on the presence of surrogate outcomes in the reports.

Results: We identified thirty-four methodological guidelines, twenty of them addressing the issue of outcome parameter choice and the problematic of surrogate outcomes. Overall HTA agencies call on caution regarding the reliance on surrogate outcomes. None of the agencies has provided a list or catalog of acceptable and validated surrogate outcomes. We extracted the outcome parameter of 140 HTA reports. Only around half of the reports determined the outcomes for the assessment prospectively. Surrogate outcomes had been used in 62 percent of the reports. However, only 3.6 percent were based upon surrogate outcomes exclusively. All of them assessed diagnostic or screening technologies and the surrogate outcomes were predominantly test characteristics.

Conclusions: HTA institutions seem to agree on a cautious approach to the use of surrogate outcomes in technology assessment. Thorough assessment of health technologies should not rely exclusively on surrogate outcomes.

Hide All
1. Antes G, Jöckel KH, Kohlmann T, Raspe H, Wasem J. Kommentierende Synopse der Fachpositionen zur Kosten-Nutzenbewertung für Arzneimittel. Erstellt im Auftrag des Bundesministeriums für Gesundheit. Freiburg, Essen: Greifswald, Kiel; 2007.
2. Australian Government – Department of Health and Aging. Guidelines for preparing submissions to the Pharmaceutical Benefits Advisory Committee (Version 4.1). Canberra: Commonwealth of Australia; 2006.
3. Biomarkers Definition Working Group. Biomarkers and surrogate end points: Preferred definitions and conceptual framework. Clin Pharmacol Ther. 2001;69:8995.
4. Bucher HC, Guyatt GH, Cook DJ, Holbrook A, McAlister FA. Users' guides to the medical literature: XIX. Applying clinical trial results. A. How to use an article measuring the effect of an intervention on surrogate end points. Evidence-Based Medicine Working Group. JAMA. 1999;282:771778.
5. Canadian Agency for Drugs and Technologies in Health. Guidelines for the economic evaluation of health technologies: Canada. Ottawa: Canadian Agency for Drugs and Technologies in Health; 2006.
6. Cleemput I, Crott R, Vrijens F, Huybrechts M, Van Wilder P, Ramaekers D. Recommandations provisoires pour les évaluations pharmacoéconomiques en Belgique. Bruxelles: Centre fédéral d'expertise des soins de santé (KCE); 2006.
7. Committee of Principal Investigators. A co-operative trial in the primary prevention of ischaemic heart disease using clofibrate: Report from the Committee of Principal Investigators. Br Heart J. 1978;40:10691118.
8. Draborg E, Gyrd-Hansen D, Poulsen PB, Horder M. International comparison of the definition and the practical application of health technology assessment. Int J Technol Assess Health Care. 2005;21:8995.
9. Dretzke J, Cummins C, Sandercock J, Fry-Smith A, Barrett T, Burls A. Autoantibody testing in children with newly diagnosed type 1 diabetes mellitus. Health Technol Assess. 2004;8:1204.
10. Elston J, Taylor RS. Use of surrogate outcomes in cost-effectiveness models: A review of United Kingdom health technology assessment reports. Int J Technol Assess Health Care. 2009;25:613.
11. Fleming TR, de Mets DL. Surrogate end points in clinical trials: Are we being misled? Ann Intern Med. 1996;125:605613.
12. Food and Drug Administration. New drug, antibiotic and biological drug product regulations: Accelerated approval. Proposal Rule. 57 Federal Register 13234-13242. Washington; 1992.
13. Fryback DG, Thornbury JR. The efficacy of diagnostic imaging. Med Decis Making. 1991;11:8894.
14. Health Care Insurance Board. Guidelines for pharmacoeconomic research, updated version. Diemen: College voor zorgverzekeringen; 2006.
15. Heidenreich PA, Lee TT, Massie BM. Effect of beta-blockade on mortality in patients with heart failure: A meta-analysis of randomized clinical trials. JAMA. 1997;30:2734.
16. HTAi Policy Forum Working Group on Surrogate Outcomes (2008). Call for expressions of interest and comments. September 2008.
17. Institut für Qualität und Wirtschaflichkeit im Gesundheitswesen. Allgemeine Methoden. Version 3.0 vom 27.05.2008. Cologne: Institut für Qualität und Wirtschaflichkeit im Gesundheitswesen; 2008.
18. Lavis JN, Wilson MG, Grimshaw J, et al. Towards optimally packaged and relevance assessed health technology assessments. Report submitted to the Canadian Agency for Drugs and Therapeutics in Healthcare. Hamilton: McMaster University; 2007.
19. Makni H, St-Hilaire C, Robb L, Larouche K, Blancquaert I. Tandem mass spectrometry and neonatal blood screening in Quebec. Montreal: AETMIS; 2007.
20. Mangiapane S, Velasco Garrido M. Surrogate endpoints for the assessment of the benefit of health technologies. Cologne: DIMDI; 2009 (in press).
21. Medical Services Advisory Committee. Funding for new medical technologies and procedures: Application and assessment guidelines. Canberra: Commonwealth of Australia; 2005.
22. MERIT-HF Study Group. Effect of metoprolol CR/XL in chronic heart failure: Metoprolol CR/XL randomized intervention trial in congestive heart failure. (MERIT-HF). Lancet. 1999;353:20012007.
23. Mundy L, Merlin T. Ultrafast magnetic resonance imaging (MRI) for patients undergoing conventional MRI. Horizon scanning prioritising summary – Volume 2. Canberra: Commonwealth of Australia; 2003.
24. National Institute of Health and Clinical Excellence. Guidance for manufacturers and sponsors. London: National Institute for Clinical Excellence; 2001.
25. National Institute for Health and Clinical Excellence. Peginterferon alfa and ribavirin for the treatment of mild chronic hepatitis C. London: National Institute for Clinical Excellence; 2006.
26. Norwegian Medicines Agency. Norwegian guidelines for pharmacoeconomic analysis in connection with applications for reimbursement. Oslo: Statens legemiddelverk; 2005.
27. Pharmaceutical Benefits Board. General guidelines for economic evaluations from the pharmaceutical benefits board. Stockholm: TLV; 2003.
28. Pharmaceutical Management Agency. Recommended methods to derive clinical inputs for proposals to PHARMAC. Christchurch; Pharmaceutical Management Agency Ltd; 2005.
29. Psaty BM, Weiss NS, Furberg CD, et al. Surrogate end points, health outcomes and the drug-approval process for the treatment of risk factors for cardiovascular disease. JAMA. 1999;282:786790.
30. Sarria-Santamera A, Timoner-Aguilera J. Assessment of the effectiveness of health promotion and disease prevention technologies. Madrid: Agencia de Evaluación de Tecnologías Sanitarias; 2002.
31. Shepherd J, Jones J, Hartwell D, et al. Interferon alfa (pegylated and nonpegylated) and ribavirin for the treatment of mild chronic hepatitis C – a systematic review and economic evaluation. Health Technol Assess. 2007;11:1224.
32. Stürzlinger H, Fröschl B, Genser D. Evaluation of optical coherence tomography in the diagnosis of age related macular degeneration compared with fluorescence angiography. Cologne: DIMDI; 2007.
33. Surrogate to Final Outcome Working Group. Report of the Surrogate to Final Outcome Working Group to the Pharmaceutical Benefits Advisory Committee: A framework for evaluating proposed surrogate measures and their use in submissions to PBAC. Canberra: 2008.$File/STFOWG%20paper%20FINAL.pdf
Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

International Journal of Technology Assessment in Health Care
  • ISSN: 0266-4623
  • EISSN: 1471-6348
  • URL: /core/journals/international-journal-of-technology-assessment-in-health-care
Please enter your name
Please enter a valid email address
Who would you like to send this to? *


Type Description Title
Supplementary Materials

Velasco Supplementary Material

 Word (183 KB)
183 KB


Full text views

Total number of HTML views: 3
Total number of PDF views: 26 *
Loading metrics...

Abstract views

Total abstract views: 195 *
Loading metrics...

* Views captured on Cambridge Core between September 2016 - 24th November 2017. This data will be updated every 24 hours.